Article Figures & Data
Figures
- Figure 1.
Organization of the diencephalon and of prosencephalic networks. A, Proposed divisions of the diencephalon by Herrick (Herrick, 1910). B, Model of circuitries involving the basal ganglia (top) and the medial zone nuclei of the hypothalamus (bottom). Both involve loop pathways with the thalamus and the cortex. The descending projections of the basal ganglia are classically divided into direct, indirect, and hyperdirect pathways. Such pathways for the medial zone nuclei of the hypothalamus have not yet been identified. BN: basal nuclei; CPu: caudoputamen nucleus; Ctx: cerebral cortex; GPe: globus pallidus, external part; GPi: globus pallidus, internal part; HYP: hypothalamus; PAG: periaqueductal gray; PBN: parabrachial nuclei; PPN: pedunculopontine nucleus; SC: superior colliculus; SNr: substantia nigra; reticular part; STN: subthalamic nucleus; TH: thalamus.
- Figure 2.
Development of the posterior hypothalamus. A–C, Pictures reprinted from the Allen Brain Institute (image credit: Allen Institute; 2020 Allen Institute for Brain Science; Allen Brain Atlas: Mouse Brain; available from http://mouse.brain-map.org/experiment/show/100092704, http://mouse.brain-map.org/experiment/show/100029214, and http://mouse.brain-map.org/experiment/show/100030632) and illustrating the distribution of genes coding for the morphogenic proteins Shh and Wnt8b on sagittal sections of embryonic brains (embryonic stages 11.5 or 13.5). D–F, Pictures reprinted from the Allen Brain Institute (image credit: Allen Institute; available from: http://mouse.brain-map.org/experiment/show/100093267, http://mouse.brain-map.org/experiment/show/100076539, and http://mouse.brain-map.org/experiment/show/100030677) and illustrating the distribution of the neuronal progenitors Nkx2.1, Lmx1a, and En1 on sagittal sections of the embryonic mouse brain. G–H, Pictures reprinted from the Allen Brain Institute (image credit: Allen Institute; available from: http://mouse.brain-map.org/experiment/show/100026263 and http://mouse.brain-map.org/experiment/show/100076531) to illustrate the embryonic distribution of the postmitotic transcription factor Pitx2 and the enzyme GAD. I, Line drawing summarizing the division of the embryonic prosencephalon and the distribution of Nkx2.1 (blue and red) and Lmx1a (green and red). J, Diagram illustrating the distribution of transcription factors involved in the differentiation of the posterior hypothalamus. The development of the ventral mesencephalon/posterior hypothalamic continuum depends on the action of morphogenetic proteins such as SHH. However, the expression domain of Wnt8b is specific of the posterior hypothalamus. The posterior hypothalamic anlage is characterized by the expression of hypothalamic (Nkx2.1, Dbx1) and mesencephalic (Lmx1a, Foxa2) neuronal progenitor genes. Some postmitotic transcription factors are also common to the mesencephalon, but then each nucleus of the posterior hypothalamus necessitates the action of specific transcription factors such as Barhl1 for the STN or Lhx5 for the MBO. Finally, the posterior hypothalamic region is massively glutamatergic while adjacent territories contain a mix of GABAergic and glutamatergic neurons. ANT: presumptive anterior area of the hypothalamus; DMH: dorsomedial nucleus hypothalamus; Glu: glutamate; dPal: dorsal pallium; mPal: medial pallium; HYP: hypothalamus; LHA: lateral hypothalamic area; MBO: mammillary nuclei; MES: mesencephalon; MesDA: DAergic ventral mesencephalon: mPal: medial pallium; PAL: pallidum; PO: presumptive preoptic area; POST: presumptive posterior hypothalamic area; PTH: prethalamus (ventral thalamus); SN: substantia nigra; STN: subthalamic nucleus; TEL: telencephalon; TH: thalamus; TUB: presumptive tuberal hypothalamic area; VMH: ventromedial hypothalamic nucleus hypothalamus; VTA: ventral tegmental area; zli: zona limitans intrathalamica.
- Figure 3.
Architecture of the glutamaergic posterior hypothalamus. A, Line drawing to illustrate the nuclear parcellation of the glutamatergic posterior hypothalamus in the rat. The pink nuclei are glutamatergic. B–E, Pictures reprinted from the Allen Brain Institute (image credit: Allen Institute; 2020 Allen Institute for Brain Science; Allen Brain Atlas: Mouse Brain; available from http://mouse.brain-map.org/experiment/show/79591669) to illustrate the distribution of GAD2 in the posterior hypothalamus of the mouse. ARH: arcuate nucleus of the hypothalamus; CbN: calbindin nucleus; cpd: cerebral peduncle; fx: fornix; LHA: lateral hypothalamic area hypothalamus; lht: lateral hypothalamic tract; LM: lateral mammillary nucleus; MM: medial mammillary nucleus; mtt: mammillothalamic tract; NG: nucleus gemini; PH: posterior hypothalamic nucleus; pm: principal mammillary tract; PMd: dorsal premammillary nucleus; PMv: ventral premammillary nucleus; PSTN: para-STN; SNr: substantia nigra, reticular part; STN: subthalamic nucleus; SUM: supramammillary nucleus; VTA: ventral tegmental area; ZI: zona incerta.
- Figure 4.
Line drawing illustrating the organization of cortical projections into the glutamatergic posterior hypothalamic nuclei. See text for details. cpd: cerebral peduncle; CbN: calbindin nucleus; INS: insular cortex; lht: lateral hypothalamic tract; LM: lateral mammillary nucleus; mch: medial cortico-hypothalamic tract; mfb: medial forebrain bundle; MM: medial mammillary nucleus; mPFC: medial prefrontal areas cortex; NG: nucleus gemini; ORB: orbital area cortex; PA: posterior nucleus of the amygdala; PMd: dorsal premammillary nucleus; PMv: ventral premammillary nucleus; post-paraSUB: posterior and parasubiculum; PSTN: para-STN; st: stria terminalis; STN: subthalamic nucleus; SUBd: dorsal subiculum; SUBv: ventral subiculum.
- Figure 5.
The basal ganglia network. Diagram summarizing the neurochemical organization of direct, indirect, and hyperdirect pathways of the basal ganglia network. GPi and SNr are considered to be the exit points of the network toward motor structures (superior colliculus and pedunculopontine nucleus). Cer. Cortex: cerebral cortex; Glu: glutamate; GPe: globus pallidus, external part; GPi: globus pallidus, internal part; PPN: pedunculopontine nucleus; pth: pathway; SNr: substantia nigra, reticular part; STN: subthalamic nucleus; Sup Col: superior colliculus; TH: thalamus.
- Figure 6.
Subcortical input to the posterior hypothalamus. Line drawing to summarize the origin of the subcortical inputs to the glutamatergic nuclei of the posterior hypothalamus. See text for details. AHN: anterior hypothalamic nucleus; BSTif: interfascicular nucleus of the bed nuclei of the stria terminalis; BSTpr: principal nucleus of the BST; BSTrh: rhomboid nucleus of the BST; CEAm: medial part of the central nucleus of the amygdala; GPe: external part of the globus pallidus; MPN: medial preoptic nucleus; MSN: medial septal nucleus; NDB: nucleus of the diagonal band; VPant, cent, post: ventral pallidum, anterior, central, or posterior regions.
- Figure 7.
Hypothalamic circuits involving the PMd and PMv. PMd and PMv are embedded within intra hypothalamic circuits with other medial zone nuclei, including the MPN and AHN. These circuits are involved in reproductive and defensive behaviors. They are under the control of pheromonal informations from the AOB and MEA as well as from informations that originates in the ventral hippocampus (SUBv and CA1v). AHN: anterior hypothalamic nucleus; AOB: accessory olfactory bulb; BST: bed nucleus of the stria terminalis; CA1v: field CA1, Ammon’s horn ventral region; LSr: lateral septal nucleus, rostral part; LSv: lateral septal nucleus, ventral part; MEA: medial amygdalar nucleus; MPN: medial preoptic nucleus; PMd: dorsal premammillary nucleus; PMv: ventral premammillary nucleus; SUBv: ventral subiculum; VMHdm: ventromedial hypothalamic nucleus hypothalamus, dorsomedial part; VMHvl: ventromedial hypothalamic nucleus hypothalamus, ventrolateral part.
- Figure 8.
Circuit involved in pup caring and in conspecific attack. In lactating females, pheromonal and other pup cues are carried to the MPO. Projections from the MPO to the PAG and VTA are involved in pup approach and care. However, if a male approaches the pups, an attack reaction from the mother to protect the pups necessitates the PMv and VMHvl. The PMv and VMHvl also mediate intermale aggressions. Male cues are caried by MEApv and PA projections to the PMv. See Wei et al. (2021) for details. AOB: accessory olfactory bulb; BSTpr: principal nucleus of the bed nuclei of the stria terminalis; MEA: medial amygdalar nucleus; MEApv: medial amygdalar nucleus, posteroventral part; MPO: medial preoptic area; PA: posterior amygdalar nucleus; PAG: periaqueductal gray; PMv: ventral premammillary nucleus; VMHvl: ventromedial hypothalamic nucleus hypothalamus, ventrolateral part. VTA: ventral tegmental area.
- Figure 9.
Organization of circuits involving the LM and MM. A, The LM is bidirectionally connected to the DTN. It also projects into the AD of the anterior thalamus which innervates the RSP and hippocampal formation. In turn the LM is innervated by the fornix. This circuit is involved in head direction. B, The MM is bidirectionally connected with the VTN and projects into the AM and AV of the anterior thalamus. The AV innervates the RSP, ENT, and HF, but through the AM, MM can also influence frontal areas and the anterior cingulate cortex, and modulates, along hippocampal projections, the activity of indirect and hyperdirect pathways from these isocortical areas (for more details, see text and Dillingham et al., 2021). AD: anterodorsal nucleus of the thalamus; AM: anteromedial nucleus of the thalamus; AV: anteroventral nucleus of the thalamus; Cing: cingulate cortex; CPu: caudoputamen; Ctx: cortex; DTN: dorsal tegmental nucleus (Gudden); ENT: entorhinal area; GP: globus pallidus; HF: hippocampal formation; LM: lateral mammillary nucleus; LSc: lateral septal nucleus, caudal part; MM: medial mammillary nucleus; MS: medial septal nucleus; RSP: retrosplenial area; STN: subthalamic nucleus; VTN: ventral tegmental nucleus (Gudden).
- Figure 10.
Diagram summarizing the organization of the telencephalic input to the glutamatergic posterior hypothalamus and SN/VTA. The posterior hypothalamus receives convergent cortical and pallidal afferences while the SN/VTA receives striatal inputs. The GPe input to the SNr is not illustrated to keep the schema simple and as they were not addressed within this paper. Cer. Cortex: cerebral cortex; PAL: pallidum; Post. Hyp.: posterior hypothalamus; Pth: pathway; SN: substantia nigra; STR: striatum; VTA: ventral tegmental area.
Tables
Cortical compartment MO, Cing, … mPFC, INS, SUBv INS, cortico-AMY SUB, CA Striatal compartment STRd (CPu) STRv (Acb, FS, OT) STRc (CEAc, CEAl, MEA) STRm (LSN, SFN) Pallidal compartment PALd (GPe, GPi) VP (SI) PALc (BST, CEAm) PALm (MSN, NDB) Table summarizing the parcellation of the telencephalon based on the nomenclature of the Allen Brain Atlas and Swanson (Allen Institute, 2004; Swanson, 2004) with a slight modification from Barbier et al. (2020; CEAm is adjoined to the PALc, see comments in Table 2). Acb: accumbens nucleus; AMY: amygdala; BST: bed nucleus of the stria terminalis; CA: Ammon’s horn; CEAc: capsular part of the central nucleus of the amygdala; CEAl: lateral part of the central nucleus of the amygdala; CEAm: medial part of the central nucleus of the amygdala; Cing: cingulate cortex; CPu: caudoputamen; FS: fundus striatum; GPe: globus pallidus, external part; GPi: globus pallidus, internal part; INS: insular cortex; LSN: lateral septal nucleus; MEA: medial amygdalar nucleus; MO: somatomotor areas; MSN: medial septal nucleus; NDB: diagonal band nucleus; OT: olfactory tubercle; PALc: caudal pallidum; PALd: dorsal pallidum; PALm: medial pallidum; mPFC:; SFN: septofimbrial nucleus; SI: substantia innominata; STRc: caudal striatum; STRd: dorsal striatum; STRm: medial striatum; STRv: ventral striatum; SUB: subiculum; SUBv: ventral subiculum; VP: ventral pallidum.
- Table 2
Origin of telencephalic subcortical inputs to the glutamatergic nuclei of the posterior hypothalamus
Posterior hypothalamus Vent MES STN PSTN/CbN Pvfox/NG PMv PMd MBO SN VTA (1, 2, 3,
4, 5)(6, 7, 8,
9, 10, 11)(4, 12,
13, 14)(16, 17,
18, 19)(15, 16) (20, 21,
22, 23)(24, 25, 26) (4, 10, 19, 21,
26, 27, 28,
29, 30)STRIATUM Dorsal striatum (caudoputamen) + ++++ Ventral striatum (nucleus accumbens,
fundus of striatum, olfactory
tubercle)+ + ++ ++++ Medial striatum (lateral septal nucleus) + ++ Caudal striatum
(central amygdalar nucleus, capsular
and lateral parts(a))+ ++ ++ MEA(b) ++++(b) + PALLIDUM Dorsal pallidum (GP) ++++ +++ VP (c) +++
central++++
posterior+++ anterior +++ Medial pallidum +++
NDB,MPO++
MS+ Caudal pallidum ++++
BSTrh, CEAm++++
BSTpr+++
BSTif++ ++ This table was realized based on the following references: (1) Canteras et al. (1990); (2) Graybiel et al. (1994); (3) Parent and Hazrati (1995a); (4) Groenewegen and Berendse (1990); (5) Groenewegen et al. (1993); (6) Barbier et al. (2020); (7) Barbier et al. (2017); (8) Chometton et al. (2016); (9) Dong and Swanson (2003); (10) Grove (1988); (11) Dong et al. (2001); (12) Price et al. (1991); (13) Heimer et al. (1990); (14) Gaykema et al. (1990); (15) Comoli et al. (2000); (16) Dong and Swanson (2004a,b); (17) Cavalcante et al. (2014); (18) Gu et al. (2003); (19) Risold and Swanson (1997); (20) Shibata (1989); (21) Swanson and Cowan (1979); (22) Vann (2010); (23) Vann and Aggleton (2004); (24) Gonzales and Chesselet (1990); (25) Gerfen and Bolam (2016); (26) Tomimoto et al. (1987); (27) Luo et al. (2011); (28) Geisler and Zahm (2005); (29) Kaufling et al. (2009); and (30) Phillipson (1979). Commentaries about the used parcellation: although we have remained very close to the nomenclature used by the Allen Brain Atlas (Allen Institute, 2004), a few adaptations seemed necessary to us. (a) The CEA is one of the striatal-like amygdalar nuclei. However, the original cytoarchitectonic study by McDonald (McDonald, 1982) revealed that only the lateral and central parts of the CEA contain striatal-like medium spiny neurons, while the medial part do not contain such neurons. The medial part of the CEA (CEAm) receives afferences from the lateral CEA as well as from the fundus striatum (belonging to the ventral striatum), which signify that the CEAm is targeted by striatal-like structures. Furthermore, it is intensely, selectively bidirectionally connected to the PSTN adjacent to the STN. Based on these considerations, the CEAm belongs to the pallidum and not to the striatum. This assertion is also compatible with developmental data (Bupesh et al., 2011; Barbier et al., 2020). (b) The MEA is also one of the striatal-like amygdalar nuclei. Without wishing to question this hypothesis, it is necessary to make a comment. Indeed, the MEA is made of a complex collection of neurons. In particular, it contains abundant populations of glutamatergic neurons with a hypothalamic or a pallial origin (Ruiz-Reig et al., 2018). These neurons are abundant in the posteroventral part of the medial amygdalar nucleus (MEApv) which sends dense projections to the PMv (Canteras et al., 1992b). Therefore, a better characterization of the neurochemical nature of the MEA projection to the PMv is necessary to understand the organization of this complex amygdalar nucleus. (c) For practical reason only, we divided the substantia innominata/VP into the three parts: the anterior VP is deep to the olfactory tubercle. The central anterior pallidum corresponds to most of the pallidum as illustrated by Root et al. (2015); the posterior VP corresponds to the posterior substantia innominata excluded from the VP by Root et al. (2015). BSTif: interfascicular part of the bed nucleus of the stria terminalis; BSTpr: principal part of the bed nucleus of the stria terminalis; BSTrh: rhomboid nucleus of the bed nucleus of the stria terminalis; CbN: calbindin nucleus; CEAm: medial part of the central nucleus of the amygdala; MBO: mammillary body; MPO: medial preoptic area; MS: medial septal nucleus; NDB: diagonal band nucleus; NG: nucleus gemini; PMd: dorsal premammillary nucleus; PMv: ventral premammillary nucleus; PSTN: para-STN; Pvfox: Parvafox nucleus; SN: substantia nigra; STN: subthalamic nucleus; VTA: ventral tegmental area.
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